The phagocytic cells of the peripheral circulation (neutrophils and monocytes) and of the reticuloendothelial system (macrophages) provide the nonimmune host with a first line of defense against pathogenic invasion and neoplastic transformation. Phagocytes possess membrane receptors for both specific ligands and for other intrinsic surface-associated substances that allow the cells to recognize a particular invader as a first step in mediating its destruction. The interaction of receptors with these specific signal molecules triggers the phagocyte to perform its normal protective functions. Knowledge of how these signal molecules and receptors function at the cellular and molecular level may eventually provide us with the ability to compensate for genetic defects that may occur in this system. Current data suggest that the interaction of phagocyte complement (C) receptors and surface-associated intrinsic C components with C3 fragments, Factor H and the C3/C5 convertase may play a key role in the pathogenesis of infection. The purpose of the proposed research project is to investigate certain aspects of human monocyte differentiation and macrophage function that may be regulated by membrane complement (C) receptors or macrophage-endogenous C components. Purified complement components, and F(ab feet)2 and Fab feet fragments of antibodies specific for either C components or C receptors will be used as probes of specific macrophage functions. The following functions will be examined in both in vitro monocyte-derived macrophages and human peritoneal macrophages: phagocytosis of bacteria and other particulate material; killing of bacteria; absorptive endocytosis of soluble complexes; and release of toxic oxygen metabolities and lysosomal hydrolases in response to a phagocytic stimulus. The role of C receptors and both endogenous and exogenous C components in regulating the in vitro differentiation of monocytes into macrophages will also be investigated. Finally, the physiocochemical basis for the phagocytic function expressed by macrophage but not monocyte CR1 (C3b receptor) and CR3 (C3bi receptor) will be investigated.